1. Field of the Invention:
This invention relates to a method for the manufacture of organic fluorine compounds. More particularly, this invention relates to a method for the manufacture of organic fluorine compounds by the so-called halogen exchange reaction, i.e. the reaction of a chloro- or bromo-organic compound with a fluorinating agent in the medium of benzonitrile.
2. Description of Prior Arts:
The so-called halogen exchange reaction, namely the reaction of an alkali fluoride upon an aromatic halide for consequent substitution of the fluorine atom for the halogen atom has been known long to the art. Generally in this reaction, an aprotic polar solvent is used as the solvent for the reactants in use. Examples of the aprotic polar solvent are dimethyl sulfoxide (DMSO), sulfolane (TMSO.sub.2), N-dimethylformamide (DMF), N-methyl-2-pyrrolidone (NMP) and dimethyl sulfone (DMSO.sub.2). The halogen exchange reaction is carried out at a temperature not exceeding the boiling point of the solvent in use. [See, for example, Ishikawa: Journal of Synthetic Organic Chemistry, Japan, vol. 25, page 808 (1967) and M. Hudlicky: Chemistry of Organic Florine Compounds, page 112 (1976), John Wiley & Sons Press.] At times, the reaction system may incorporate therein a phase transfer catalyst such as a crown compound for the purpose of increasing the reaction velocity.
When the halogen exchange is carried out by the method described above, however, the halogens in those aromatic monohalides and aromatic polyhalides which have halogen substituents at the ortho or para positions of electron-attractive groups (such as, for example, --CN and --NO.sub.2) easily undergo halogen exchange, while halogens at meta positions do not undergo halogen exchange at all. The aromatic halides on which halogen exchange can be effected by the aforementioned method generally are limited to aromatic halides having only small numbers of halogen substituents such as those represented by the synthesis of 2,6-difluorobenzo-nitrile from 2,6-dichlorobenzonitrile described in Ishikawa: Journal of Synthetic Organic Chemistry, Japan, Vol. 27, page 174 (1969). More often than not it is difficult to effect perfect halogen exchange on polyhalides of higher orders than those mentioned above. If perfect halogen exchange is obtained somehow or other on such polyhalides, the yields are poor.
The method described above does not suit the production of m-fluorobenzonitrile and 3,5-difluorobenzonitrile respectively from m-chlorobenzonitrile and 3,5-dichlorobenzonitrile which have halogen substituents at the meta positions of cyano groups. By the same token, this method does not suit the production of 3-fluoropyridine and 2,5-difluoropyridine respectively from 3-choloropyridine and 2,5-dichloropyridine which have halogen substituents at the meta positions of the nitrogen atoms having the electron attractive property. No process is reported in literature as having provided effective production of m-fluorobenzonitrile from m-chlorobenzonitrile, 3,5-difluorobenzonitrile from 3,5-dichlorobenzonitrile, 3-fluoropyridine from 3-chloropyridine, or 2,5-difluoropyridine from 2,5-dichloropyridine by halogen exchange reaction carried out in a solvent. Such is the true status of affairs.
A case of halogen exchange effected on 2,5-dichloropyridine is reported by G. G. Finger et al in J. Org. Chem., Vol. 23, page 1666 (1963). When 2,5-dichloropyridine is subjected to halogen exchange in DMSO.sub.2 as a solvent by using potassium fluoride as a fluorinating agent, the reaction only produces 5-chloro-2-fluoropyridine and fails to afford 2,5-difluoropyridine.
Moreover, the method described above does not suit the production of pentafluorobenzonitrile and tetrafluoroisophthalonitrile respectively from pentachlorobenzonitrile and tetrachloroisophthalonitrile which are polyhalides and which have halogen substituents at the meta positons of cyano groups. It does not suit the production of pentafluoropyridine from pentachloropyridine which is a polyhalide and which has a halogen substituent at the meta position of the nitrogen atom having an electron attractive property. No process is reported in literature as having provided effective production of pentafluorobenzonitrile from pentachlorobenzonitrile, tetrafluoroisophthalonitrile from tetrachloroisophthalonitrile, or pentafluoropyridine from pentachloropyridine by halogen exchange effected in a solvent.
In fact, when pentachlorobenzonitrile is refluxed in dimethyl sulfoxide as a solvent in the presence of excess potassium fluoride for 24 hours in accordance with the method described above, the reaction produces 3,5-dichloro-2,4,6-trifluorobenzonitrile but fails to afford perfectly halogen exchanged pentafluorobenzonitrile at all. When the reaction is carried out under reflux in a solvent generally adopted in halogen exchange reaction, the results are the same as described above. The same results persist when the reaction system incorporates therein a phase transfer catalyst.
It has been ascertained by our research that for the halogen exchange reaction to be effected completely, the reaction temperature must be increased by the use of an autoclave. It has been further ascertained that when the reaction is carried out in any solvent generally adopted in the halogen exchange reaction except for benzonitrile which is specifically used for the present invention, the yield of the reaction is too low for the reaction to be economically feasible because, at elevated temperatures, the solvent undergoes decomposition or a secondary reaction with the reactants or with the product of the main reaction. M. Birchall et al report in J. Chem. Soc. (C) (1971), page 1341 a report on a method for synthesizing pentafluorobenzonitrile by treating pentachlorobenzonitrile at elevated temperatures of 300.degree. to 480.degree. C. with potassium fluoride as a fluorinating agent in an autoclave without use of a solvent. Their reaction performed at 350.degree. C. for 20 hours is reported to have yielded about 70 mol % of pentafluorobenzonitrile based on pentachlorobenzonitrile. Since this reaction uses no solvent, it proceeds with generation of heat and this heat makes control of the reaction temperature difficult. At the end of the reaction, a large amount of carbonized materials remains fast to the vessel. All considered, this method proves to be hardly feasible from the economic point of view.
No method is reported in literature as having successfully synthesized tetrafluoroisophthalonitrile by halogen exchange from tetrachloroisophthalonitrile. Only a case of halogen exchange effected on tetrachloroisophthalonitrile is reported by Ishikawa et al in Journal of Industrial Chemistry, Vol. 73, page 447 (1970). When the halogen exchange reaction is carried out in DMF as a solvent with potassium fluoride as a fluorinating agent, it barely produces 5-chloro-2,4,6-trifluoroisophthalonitrile and fails to afford perfectly substituted tetrafluoroisophthalonitrile.
Methods for producing tetrafluoroterephthalonitrile by halogen exchange of tetrachloroterephthalonitrile, a polyhalide, by using solvents of ordinary run have been suggested in French Pat. No. 1,397,521 (1965) and Japanese patent Open (Kokai) SHO No. 51(1976)-6940. Neither of these methods produce tetrafluoroterephthalonitrile in satisfactory yields. The ordinary solvents used in these methods are such that when the reaction temperature is elevated or the reaction is protracted for the purpose of improving yields, these solvents undergo decomposition or undergo secondary reaction with the reactants or with the products of main reaction only to impair yields. These methods have another disadvantage that even if the used solvents are recovered, the hardly suit commercial use. The method which effects the reaction at high temperature of 200.degree. to 400.degree. C. in an autoclave without use of a solvent finds general recognition as one approach to avoiding the drawback that such solvents are not usable at elevated temperatures. A case of halogen exchange effected on tetrachloroterephtalonitrile at 300.degree. C. in an autoclave without use of a solvent to produce tetrafluoroterephthalonitrile is reported, for example, by Ueda et al in Bull. Chem. Soc. Japan, Vol. 40, page 688. Since this reaction uses no solvent, it proceeds with generation of heat and the heat thus generated renders the control of the reaction temperature difficult. At the end of the reaction, a large amount of carbonized materials remains fast to the vessel. Thus, this method proves to be hardly feasible from the economic point of view.
R. E. Banks et al report in J. Chem. Soc., page 594 (1965) a halogen exchange reaction accomplished on pentachloropyridine in NMP as a solvent at the boiling point of this solvent. This reaction preponderantly produces 3,5-dichloro-2,4,6-trifluoropyridine and fails to produce perfectly halogen exchanged pentafluoropyridine. The solvent generally adopted for this reaction is such that when the reaction temperature is increased or the reaction time is protracted for the purpose of improving the yield of the reaction, the solvent undergoes decomposition or undergoes secondary reaction with the reactants or with the product of the main reaction only to impair the yield. This method has another disadvantage that the used solvent, even if recovered, does not suit commercial use. The solvents usable in this method have a disadvantage that they cannot be effectively used at elevated temperatures. The method which effects the reaction at elevated temperatures of 200.degree. to 500.degree. C. in an autoclave in the absence of a solvent finds general recognition as one approach to avoiding the drawback that such solvents are not usable at high temperatures. A case of halogen exchange effected on pentachloropyridine at 500.degree. C. in an autoclave in the absence of a solvent to produce pentafluoropyridine is reported by R. E. Banks et al. in J. Chem. Soc., page 594 (1965). Because this reaction uses no solvent, it proceeds with generation of heat and this heat renders the control of the reaction temperature difficult. Moreover, a large amount of carbonized materials remains fast to the vessel. Thus, this method proves to be hardly feasible from the economic point of view.